Suspected severe methemoglobinemia caused by topical application of an ointment containing benzocaine around the enterostomy.
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Biomedical subjects
Publications and source records attributed to M Hayashi.
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A 55-year-old man developed acute respiratory failure, pulmonary hypertension and left heart failure due to acute myocardial infarction. Nitric oxide (NO) inhalation improved arterial oxygenation, decreased pulmonary arterial pressure and increased cardiac output (CO), but combined use of dobutamine with NO produced increases in pulmonary arterial pressure and pulmonary capillary wedge pressure (PCWP). In this patient, amrinone decreased pulmonary arterial pressure and PCWP, and increased PaO2/FiO2 effectively while increasing CO. Combined use of inhaled NO and intravenous amrinone may have beneficial effects for a patient with acute respiratory and cardiac failure.
Intrusive trauma was experimentally applied to the tooth germ at different developmental stages in the rat first molar. The tooth germ at the earliest (postnatal day 1, initiating stage of enamel matrix formation) and the latest (postnatal day 10, calcifying stage of preformed enamel matrix) developmental stages studied showed localized enamel hypoplasia as a direct sequela of trauma. The tooth germs in which enamel matrix was rapidly thickening (postnatal days 3, 5, 7) and had not yet started to calcify showed the most intense and extensive injuries to the formation and structural organization of both enamel and dentin. As for indirect effects secondary to trauma, tooth germ dislocation was observed chiefly in tooth germs at the same developmental stages, frequently resulting in ankylosis. The present experimental model may be helpful for clarifying the histogenesis of traumatic changes in the developing tooth germ.
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OBJECTIVES: Mutational analysis of the sterol 27-hydroxylase (CYP27) gene was performed on three patients from two Japanese families who had cerebrotendinous xanthomatosis (CTX) associated with parkinsonism. METHODS: Clinical evaluations, brain MRI studies, and laboratory analyses were completed on the three patients. The CYP27 gene was analysed for mutations by PCR amplification of gene segments followed by direct sequencing. RESULTS: Two different, homozygous mutations were identified in these families. One is a novel transition, substituting T for G at Glu162 (GAG) resulting in a stop codon (TAG). The other is also a transition, substituting T for C at Arg441 (CGG) resulting in Trp (TGG). The second is located in two amino acids ahead of the heme ligand binding site (Cys443) of the protein likely rendering it non-functional. It is the most common CTX mutation in Japanese patients. CONCLUSIONS: CTX with parkinsonism is caused by mutations with a severe impact on enzyme function. The two mutations described here are likely to cause loss of function because they are chain terminating or affect an essential site in the protein.
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Pressure control of renin secretion involves a complex integration of shear stress, stretch, and transmural pressure (TP). This study was designed to delineate TP control of renin secretion with minimal influence of shear stress or stretch and to determine its mechanism. Rat juxtaglomerular (JG) cells were applied to a TP-loading apparatus for 12 h. In cells conditioned with atmospheric pressure or atmospheric pressure + 40 mmHg, renin secretion rate (RSR) averaged 29.6 +/- 3.7 and 14.5 +/- 3.3% (P < 0.05, n = 8 cultures), respectively, and active renin content (ARC) averaged 47.3 +/- 4.6 and 38.4 +/- 3.4 ng of ANG I. h(-1). million cells(-1) (P < 0.05, n = 10 cultures), respectively. Total renin content and renin mRNA levels were unaffected by TP. The TP-induced decrease in RSR was prevented by Ca(2+)-free medium and the Ca(2+) channel blocker verapamil and was attenuated by thapsigargin and caffeine, which deplete intracellular Ca(2+) stores. Thapsigargin and caffeine, but not Ca(2+)-free medium or verapamil, prevented TP-induced decreases in ARC. The adenylate cyclase activator forskolin did not modulate TP-induced decreases in RSR or ARC. These findings suggest that TP not only stimulates Ca(2+) influx but also inhibits prorenin processing through an intracellular Ca(2+) store-dependent mechanism and thus inhibits active renin secretion by JG cells.
Gamma Knife radiosurgery is an effective treatment for meningiomas. However, it may be difficult to deliver what is currently considered an optimal dose, especially if the tumor is large or adjacent to critical structures. Eleven cases are presented with a follow-up of more than 12 months where the margin dose did not exceed 10 Gy. The mean age was 48.8 years. The mean follow-up period was 35.7 months (range 21 to 57 months). The mean volume of the tumors was 9.4 cm3 (range 1.6 to 28.9 cm3). The margin dose was less than 10 Gy in all 11 cases, due to a large volume in two cases. Four tumors were close to the visual pathways. Five tumors were close to the brain stem. Imaging follow-up showed that four tumors had shrunk after radiosurgery. The remaining seven cases remained unchanged. There was no tumor growth after radiosurgery. A transient oculomotor palsy was observed in two cases after radiosurgery. It is suggested that Gamma Knife radiosurgery using lower dosage than usual is one of the options for the treatment of meningioma.
Ninety-two patients with pituitary adenomas have been treated during the last 5 years. Sixty-three of these patients had more than 6 months follow-up, and they form the basis of this report. Eighteen had non-functioning adenomas (NFA), and 36 had functioning adenomas (FA). The mean marginal dose was 22.5 Gy (NFA 19.5 Gy, FA 23.9 Gy). Control of tumor growth was achieved in 92%. A significant decrease of excessive hormone production was seen in 75.6%, and the endocrinopathy normalization rate was 26.7%. Post-radiosurgical complications were seen in 4.7%.
Transgenic mice with deletion of the GDF-9 (growth differentiation factor-9) gene are characterized by the arrest of ovarian follicle development at the primary stage. Based on the hypothesis that GDF-9 is important for early follicle development, we isolated rat GDF-9 complementary DNA (cDNA) and generated recombinant GDF-9 protein to study its physiological role. Using bacteria-derived GDF-9-glutathione S-transferase (GST) fusion protein, specific antibodies to the mature form of GDF-9 was generated. Immunohistochemical staining of ovarian sections indicated the localization of GDF-9 protein in the oocyte of primary, secondary and preantral follicles, whereas immunoblotting demonstrated the secretion of GDF-9 by mammalian cells transfected with GDF-9 cDNAs. Recombinant GDF-9 was shown to be an N-glycosylated protein capable of stimulating early follicle development. Growth of preantral follicles isolated from immature rats was enhanced by treatment with either GDF-9 or FSH whereas the combined treatment showed an additive effect. In addition, treatment with GDF-9, like forskolin, also stimulated inhibin-alpha content in explants of neonatal ovaries. In contrast, the stimulatory effects of GDF-9 were not mimicked by amino-terminal tagged GDF-9 that was apparently not bioactive. Thus, the present study demonstrates the important role of GDF-9 in early follicle growth and differentiation. The availability of recombinant bioactive GDF-9 allows future studies on the physiological role of GDF-9 in ovarian development in vivo.
A new antibiotic, korormicin, isolated from a marine bacterium Pseudoalteromonas sp. F-420, was found to strongly inhibit the respiratory chain-linked Na+-translocating NADH-quinone reductase (NQR) from the marine Vibrio alginolyticus. Similar to 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), korormicin specifically inhibited the Na+-dependent reaction in the NQR complex that is directly coupled to the extrusion of Na+ from the cells. Both korormicin and HQNO acted as purely noncompetitive inhibitors with regard to Q-1, and the inhibitor constants were estimated to be 82 pM and 0.3 microM, respectively. Mutual exclusiveness of korormicin and HQNO was analyzed by kinetic methods, which indicated that a part of the binding site of korormicin and HQNO overlapped, preventing a simultaneous binding of the two inhibitors to the NQR complex. The site of Ag+ inhibition was the initial reaction of the NQR complex catalyzed by Nqr6 subunit. The time courses of Ag+ inhibition and the release of FAD indicate that the Ag+-denatured Nqr6 subunit gradually releases FAD.
Cycloprodigiosin hydrochloride (cPrG*HCl) is a stable fluorescent red pigment obtained from the marine bacterium Pseudoalteromonas denitrificans. It was found that the compound was incorporated into Plasmodium falciparum cells upon incubation and exhibited a potent antimalarial activity with the concentration required for 50% of the activity being 11 nM, which is stronger than that of chloroquine, a well-known antimalarial agent. The compound did not affect growth rate of mammalian cells. Antimalarial activity of cPrG*HCl was also observed in vivo. These results indicate that cPrG*HCl is a potent antimalarial drug.
This report describes a 49-year-old male with concealed Wolff-Parkinson-White syndrome in whom a true uncommon atrial flutter suddenly emerged 2 weeks after successful catheter ablation of a left-sided accessory pathway. The earliest atrial activation during the atrial flutter was recorded at the posterolateral mitral annulus 2 cm proximal to the previous successful ablation site for the accessory pathway. Two applications of radiofrequency (RF) current directed at the supravalvular mitral annulus could not terminate the atrial flutter. A subsequent delivery of RF current directed at the subvalvular annulus, where a local fragmented potential preceded the earliest atrial activation, eliminated the atrial flutter.
Angiotensin converting enzyme inhibitors (ACEI) are known to inhibit the progression of established renal failure. The aim of this study was to compare the efficacy of an ACEI and an AT1 receptor antagonist (AT1R-Ant) in preventing the development of renal disease, at an early stage of hypertensive nephrosclerosis. SHRSP/Izm rats (n = 61) were treated from 10 wk until 22 wk with the ACEI delapril (40 mg/kg/d) or the AT1R-Ant candesartan cilexetil (1 mg/kg/d). Proteinuria, and structural/ultrastructural changes were assessed at 14 and 22 wk. Treatment with either agent resulted in reductions in blood pressure and cardiovascular hypertrophy. Neither proteinuria nor major renal histological changes were evident at 14 wk. At 22 wk, however, proteinuria accompanied by nephrosclerotic changes was seen in the untreated SHRSP/Izm. Treatment with either ACEI or AT1R-Ant resulted in similar reductions in proteinuria (untreated, 32.2 +/- 7.4; delapril-treated, 5.5 +/- 1.2; candesartan-treated, 3.9 +/- 0.3 mg/100 g/d). Prominent sclerosis of small-to-medium sized renal arteries was seen in the untreated SHRSP/Izm at 22 wk, but was similarly attenuated by the ACEI and AT1R-Ant. The glomerular ultrastructure was comparable between the two groups. No significant changes in renal AT1a or AT1b receptor subtype mRNA expression were seen throughout the course of the study. In contrast, a decrease in AT2 receptor mRNA was seen in the drug-treated groups at 14 wk but not at 22 wk. These results suggest that both ACEI and AT1R-Ant have similar efficacy in attenuating the onset of renal injury in early hypertensive nephrosclerosis, and that treatment with either agent is associated with a transient decrease in AT2 receptor mRNA expression.
DNA synthesis was effectively inhibited by antisense oligonucleotide A1 complementary to the BamHI-H gene family in Marek's disease virus (MDV)-derived lymphoblastoid MDCC-MSB1 cells. When a cell cycle distribution of a total cell population was analyzed by flow cytometry, the proportion of S-phase cells increased in the cell populations by treatment with oligonucleotide A1. Approximately 60-70% of the cells appeared in the S phase for 24 and 36 hr of incubation in the presence of oligonucleotide A1 (20-30% in the untreated control cells). The inhibition of cell cycle progression by treatment with oligonucleotide A1 was reversible. When the cells were treated with 5 microM aphidicolin for 12 hr, a similar pattern of cell cycle distribution was observed to that obtained after treatment with oligonucleotide A1. Aphidicolin is an inhibitor of cellular DNA polymerase alpha, and it halts progression of the cell cycle at the G1/S border or early S phase. When the cells were treated with aphidicolin for 12 hr and subsequently incubated with oligonucleotide A1, no significant difference was observed in the cycle phase distribution of cells in the presence and absence of oligonucleotide A1. In contrast, when the cells were treated with oligonucleotide A1 for 12 hr and subsequently incubated with aphidicolin, the cell cycle did not progress from the G1/S border or early S phase to the next phase.
The effect of X-irradiation on the progression of the cell cycle in cell lines from LEC and WKAH rats was investigated by a flow cytometer. When the cells were exposed to 5 Gy of X-rays at S phase, the proportion of S-phase cells in both cell populations decreased with incubation time and that of G2/M-phase cells was approximately 80% at 6 hr post-irradiation. At 12 hr post-irradiation, approximately 45% of the WKAH rat cells appeared in the G1 phase. However, 80-90% of LEC rat cells remained in the G2/M phase and less than 5% in the G1 phase during 6-12 hr post-irradiation. Thus, the LEC rat cells irradiated at S phase remained in the G2/M phase for at least 6 hr longer than did the WKAH rat cells.
We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.